Vitamin D is known to be important in the regulation of calcium metabolism in animals and man. See, Harrison's Principals of Internal Medicine: Part Eleven, "Disorders of Bone and Mineral Metabolism, Chapter 335," E. Braunwald, et al., (eds.), McGraw-fill, New York, 1987, pp. 1860-1865. The two most commonly known, useful forms of vitamin D are vitamin D.sub.3 and vitamin D.sub.2. Vitamin D.sub.3 is synthesized endogenously in the skin of animals and man, whereas vitamin D.sub.2 is the form of vitamin D supplied by plants. Vitamin D.sub.2 differs from vitamin D.sub.3 in that it contains a double bond between C22 and C23 and further contains a C24-methyl group. In man and rats, vitamin D.sub.3 and vitamin D.sub.2 have equivalent biopotency.
Vitamin D.sub.4, also known as irradiated 22,23-dihydroergosterol or 22,23-dihydro vitamin D.sub.2 or 22,23-dihydroergocalciferol, differs from vitamin D.sub.3 in that it contains a C24 methyl group. Vitamin D.sub.4 was first described in 1936. See, Grab, W., Z. Physiol. Chem., 243: 63 (1936); McDonald, F. G., J. Biol. Chem., 114: IVX (1936). See also, Windaus, A. and Trautmann, G., Z. Physiol. Chem., 247: 185-188 (1937). These references report some disagreement as to the level of biological activity of the vitamin suggesting that in the rat, vitamin D.sub.4 is one-third or three-fourths as active as vitamin D.sub.3 and in the chick, either one-tenth or one-fifth as active as vitamin D.sub.3.
A more definitive study of the biological activity of vitamin D.sub.4 was made by DeLuca, et al., in 1968. DeLuca, et al., Arch. Biochem. Biophys., 124: 122-128 (1968). There, the authors confirmed that vitamin D.sub.4 was less active than vitamin D.sub.3. DeLuca, et al., report that, in their hands, vitamin D.sub.4 is two-thirds as active as vitamin D.sub.3 or vitamin D.sub.2 in the rat, and one-fifth as active as vitamin D.sub.3 in the chick.
DeLuca, et al., make reference to the fact that "[t]he synthesis of vitamin D.sub.4 has apparently been little used since it was first described by Windhaus and Trautmann," and comment, "[t]his is perhaps due to the fact that vitamin D.sub.4 is only of academic interest."
To applicants' knowledge, vitamin D.sub.4 has remained "only of academic interest" as applicants are unaware of any further study of vitamin D.sub.4 since that reported by DeLuca, et. al. In fact, The Merck Index states with respect to vitamin D.sub.4, "Its biological activity seems doubtful." Merck Index, S. Budavari (ed.), 11th ed., Merck & Co., Rahway, N.J., (1989) pp. 1579, #9930.
Since DeLuca, et. al., discovered the active form of vitamin D.sub.3, 1,25-dihydroxy vitamin D.sub.3, (U.S. Pat. No. 3,697,559) and its synthetic precursor, 1.alpha.-hydroxy vitamin D.sub.3, (U.S. Pat. No. 3,741,996), most interest has centered on developing therapeutic uses of these active vitamin D.sub.3 metabolites. Unfortunately, while the vitamin D.sub.3 metabolites held great promise as therapeutic agents, this promise has never been fully realized because of the extreme toxicity of these agents. For example, toxicity limits the efficacy of vitamin D.sub.3, its active forms and analogs, to prevent bone loss or restore lost bone. Many studies indicate that at dosages required for these agents to be effective in bone loss prevention or restoration, hypercalcemia and hypercalciuria are problems. It has been reported that 1.alpha.-hydroxy vitamin D.sub.3 at a daily dose of 2 .mu.g/day (which has been shown in some studies to be effective in preventing loss of bone) causes toxicity in approximately 67% of patients. What is needed is a biopotent vitamin D metabolite of low toxicity, such that the drug is practical as a therapeutic agent.